Systems and methods for molecular diagnostics

• US 10,427,162 B2
• Filed: 12/21/2016
• Issued: 10/01/2019
• Est. Priority Date: 12/21/2016
• Status: Active Grant

• Current Assignee: QuanDx, Inc.
• Original Assignee: QuanDx, Inc.
• Inventors: Lei, Xiaojun, Yuan, Yuan, Xu, Qian, Fleming, Paul, Hayes, Ronan, Lewis, Brian, Richardson, Bruce
• Primary Examiner(s): Fritchman, Rebecca M
• Application Number:
  US15/385,873
• Publication Number:
  US 20180169658A1
• Time in Patent Office: 1,014 Days
• Field of Search: 422500
• CPC Class Codes: B01L 2200/0631 Purification arrangements, e.g. solid phase extraction [SPE]
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/022 Transponder chips
• CPC Class Codes: B01L 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 3/0275 Interchangeable or disposable dispensing tips
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046

Abstract

The present disclosure provides systems, devices and methods associates with processing and analyzing samples for molecular diagnostics. The system may process samples using assay cartridges including sample preparation modules and PCR modules. The system may include thermal cycler modules and optics modules to detect the specific nucleic acid sequences in the samples.

Claims

1. A sample preparation module for an assay cartridge used in a PCR-based molecular diagnostic device, said sample preparation module comprising an elongated body which comprises a sample loading well of an asymmetric shape where a sample is loaded before nucleic acid is extracted from the sample, said PCR-based molecular diagnostic device comprising an automatic dispense system to transfer the sample using a pipette, wherein the sample loading well comprises

a generally vertical wall around the sample loading well,

a tilted cone shape bottom having a deepest portion,

a sample loading well inlet covered by a removable cap, and

a sample collecting channel having a sample loading well outlet at its top end and a fluid collecting area at its bottom end,

wherein the removable cap has a cap inlet covered by a cap inlet septum having an inlet slit,

wherein the sample loading well outlet is covered by a sample loading well outlet septum having an outlet slit,

wherein the fluid collecting area is at the deepest portion of the bottom,

wherein the pipette is capable of adding the sample to the sample loading well through the sample loading well inlet, and

wherein the pipette is capable of collecting the nucleic acid from the fluid collecting area through the sample loading well outlet.

2. The sample preparation module of claim 1, further comprising a formalin-fixed paraffin-embedded (FFPE) capture insert removable from the sample loading well, wherein the removable cap comprises a plunger.

3. The sample preparation module of claim 1, wherein the elongated body further comprises a purification well.

4. The sample preparation module of claim 3, wherein the purification well contains magnetic microparticles capable of binding to nucleic acid.

5. The sample preparation module of claim 1, wherein the elongated body further comprises one or more reagent compartments.

6. The sample preparation module of claim 1, wherein the elongated body further comprises a pipette tip holder.

7. The sample preparation module of claim 6, wherein the pipette tip holder is preloaded with a pipette tip.

8. An assay cartridge for a PCR-based molecular diagnostic device, said PCR-based molecular diagnostic device comprising an automatic dispense system to transfer the sample using a pipette, said assay cartridge comprising:

a sample preparation module comprising an elongated body which comprises a sample loading well of an asymmetric shape where a sample is loaded before nucleic acid is extracted from the sample, wherein the sample loading well comprises

a generally vertical wall around the sample loading well,

a tilted cone shape bottom having a deepest portion,

a sample loading well inlet covered by a removable cap, and

a sample collecting channel having a sample loading well outlet at its top end and a fluid collecting area at its bottom end,

wherein the removable cap has a cap inlet covered by a cap inlet septum having an inlet slit,

wherein the sample loading well outlet is covered by a sample loading well outlet septum having an outlet slit,

wherein the fluid collecting area is at the deepest portion of the bottom,

wherein the pipette is capable of adding the sample to the sample loading well through the sample loading well inlet, and

wherein the pipette is capable of collecting the nucleic acid from the fluid collecting area through the sample loading well outlet; and

a PCR module,

wherein the sample preparation module and the PCR module is detachably coupled.

9. The assay cartridge of claim 8, wherein the sample preparation module and the PCR module is detachably coupled through a snap.

10. The assay cartridge of claim 8, further comprising a marking element.

11. The assay cartridge of claim 10, wherein the marking element is selected from the group consisting of a barcode, a dot code, a radio frequency identification tag (RFID) and a direct reading electronic memory.

12. The assay cartridge of claim 8, wherein the PCR module comprises

a push well capable of being loaded with the nucleic acid extracted in the sample preparation module,

at least one reaction well, and

a microfluidic channel connecting a first opening at the bottom of the push well and a second opening at the top of the reaction well.